Restriction of hepatitis B virus replication by c-Abl-induced proteasomal degradation of the viral polymerase
Hou, Lidan1,2; Zhao, Jie3; Gao, Shaobing1,4; Ji, Tong3; Song, Tianyu1,2; Li, Yining1; Wang, Jingjie1; Geng, Chenlu1; Long, Min1; Chen, Jiang3; Lin, Hui3; Cai, Xiujun3; Cang, Yong2
2019-02
Source PublicationSCIENCE ADVANCES
ISSN2375-2548
Volume5Issue:2
Status已发表
DOI10.1126/sciadv.aau7130
AbstractAbout 257 million people with chronic infection of hepatitis B virus (HBV) worldwide are at high risk of developing terminal liver diseases. Reactivation of virus replication has been frequently reported in those patient populations receiving imatinib (an Abl kinase inhibitor) or bortezomib (a proteasome inhibitor) to treat concurrent diseases, but the underlying mechanism for this reactivation is unknown. We report that the HBV polymerase protein is recruited by Cdt2 to the cullin-RING ligase 4 (CRL4) for ubiquitination and proteasome degradation and that this process is stimulated by the c-Abl nonreceptor tyrosine kinase. Genetic ablation of the Abl-CRL4(cdt2) axis or pharmaceutical inhibition of this process stabilizes HBV polymerase protein and increases viral loads in HBV-infected liver cancer cell lines. Our study reveals a kinase-dependent activation of CRL4 ubiquitin ligase that can be targeted for blocking HBV replication.
Indexed BySCI ; EI
Language英语
Funding ProjectNational Natural Science Foundation[91429302]
WOS Research AreaScience & Technology - Other Topics
WOS SubjectMultidisciplinary Sciences
WOS IDWOS:000460145700034
PublisherAMER ASSOC ADVANCEMENT SCIENCE
EI Accession Number20190706500651
EI KeywordsAmino acids ; Cell culture ; Enzymes
EI Classification NumberBiology:461.9 ; Organic Compounds:804.1
WOS KeywordMYELOMA DRUG LENALIDOMIDE ; X-PROTEIN ; LEUKEMIA PATIENT ; REACTIVATION ; BINDING ; DESTRUCTION ; INFECTION ; INHIBITORS ; COMPLEX ; DDB1
Original Document TypeArticle
Citation statistics
Cited Times:12[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Identifierhttps://kms.shanghaitech.edu.cn/handle/2MSLDSTB/30555
Collection生命科学与技术学院_PI研究组_仓勇组
Corresponding AuthorCang, Yong
Affiliation1.Zhejiang Univ, Life Sci Inst, Hangzhou 310058, Zhejiang, Peoples R China
2.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 201210, Peoples R China
3.Zhejiang Univ, Sir Run Run Shaw Hosp, Coll Med, Dept Gen Surg, Hangzhou 310058, Zhejiang, Peoples R China
4.Zhengzhou Univ, Affiliated Canc Hosp, Zhengzhou 450008, Henan, Peoples R China
First Author AffilicationSchool of Life Science and Technology
Corresponding Author AffilicationSchool of Life Science and Technology
Recommended Citation
GB/T 7714
Hou, Lidan,Zhao, Jie,Gao, Shaobing,et al. Restriction of hepatitis B virus replication by c-Abl-induced proteasomal degradation of the viral polymerase[J]. SCIENCE ADVANCES,2019,5(2).
APA Hou, Lidan.,Zhao, Jie.,Gao, Shaobing.,Ji, Tong.,Song, Tianyu.,...&Cang, Yong.(2019).Restriction of hepatitis B virus replication by c-Abl-induced proteasomal degradation of the viral polymerase.SCIENCE ADVANCES,5(2).
MLA Hou, Lidan,et al."Restriction of hepatitis B virus replication by c-Abl-induced proteasomal degradation of the viral polymerase".SCIENCE ADVANCES 5.2(2019).
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